We are requesting funding for an In Vivo micro-computerized tomography (<CT) system from SCANCO Medical (Viva-CT 40) to be sited in the barrier animal facility at the Harvard School of Public Health (HSPH) for use by the biomedical research community at HSPH and the Harvard School of Dental Medicine (HSDM) in Boston. This system consists of the Viva-CT 40 scanner, two computers for data acquisition and analysis, and an isoflurane based anesthesia system. The In Vivo <CT will be primarily used to evaluate genetically engineered mice in established and developmental models of bone loss and accrual as well as arthritis. Bone and joints are remarkable biomaterials that model and remodel to grow, preserve structural integrity and adapt to stress. This dynamic process is controlled by bone forming osteoblasts, bone resorbing osteoclasts and cartilage matrix secreting chondrocytes. An imbalance between catabolic and anabolic activity within bone and joints contributes to some of the most common public health problems including osteoporosis, arthritis and cancer. Much has been learned about the molecular control of bone remodeling by the analysis of genetically engineered mouse models of these human conditions. Importantly, humans and rodents share the majority of pathways that control osteoblast, osteoclast and chondrocyte behavior. The relatively recent availability of In Vivo <CT machines has made it possible for biologists interested in the skeletal system to follow skeletal parameters in the same mouse over time. This technique could vastly improve the quality of the currently funded studies from the major (Glimcher, Olsen and Baron) and minor (Hotamisligil, Aliprantis, Jones, Lankse, and Li) users included in this proposal who each use mouse genetics to probe the skeletal system. The Viva CT 40 will be incorporated into the existing <CT facility at HSDM where we now routinely perform Ex Vivo <CT. A strong commitment from the administration at HSPH completes this application by assuring a long- term service contract for the instrument as well as support for technical assistance. In summary, the Viva CT 40 will allow us to longitudinally compare bone parameters in the same mouse over time thereby substantially reducing the number of animals needed for robust validation of preclinical studies and facilitating the timely completion of our PHS funded projects. Public Health Relevance: Ten faculty members at HSPH and HSDM who each use mouse genetics to probe the skeletal system are requesting funding for an In Vivo CAT scan system from SCANCO Medical (Viva-CT 40). This instrument allows the evaluation of individual genetically engineered mice in models of bone loss and accrual over time and will provide robust validation of preclinical models of human skeletal diseases such as osteoporosis and arthritis.